Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn’s disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas.

Background: Previous work on inflammatory bowel disease (IBD) revealed changes in the abundance of colonic stromal subsets during intestinal inflammation. However, it is currently unknown whether these stromal cell subset changes are also reflected in different IBD mouse models and how commonly used IBD therapies affect stromal cell subset composition. Methods: Stromal subset markers CD55, C-X-C motif chemokine 12 (CXCL12), podoplanin (PDPN), CD90, and CD73 were analyzed by flow cytometry in 3 mouse models for IBD, namely interleukin (IL)-10 knockout (KO), dextran sulfate sodium-induced, and T-cell transfer model for colitis. Next, the effects of IBD therapies on the stromal subset composition were studied. In vitro experiments were performed to study the interaction between stromal cell subsets and epithelial/immune cells. Results: The colitis-induced changes in the abundance of stromal cell subsets differed considerably between the 3 colitis mouse models. Interestingly, treatment with IBD medication affected specific stromal subsets in a therapy and model-specific manner. In vitro experiments showed that specific stromal subsets affected epithelial wound healing and/or T-cell activation. Conclusions: The relative abundance changes of stromal cell subsets during experimental colitis differ between 3 established colitis models. Treatment with IBD therapies influences stromal subset abundance, indicating their importance in IBD pathogenesis, possibly through affecting epithelial migration, and T-cell activation.